SS-31 Case Study

In the United Kingdom alone, 150 new born children per year suffer from life threatening, mitochondrial diseases. These diseases vary in severity from person to person, making them difficult to diagnose, and they inflict an array of ailments such as neurological problems, muscle weakness, visual or auditory impairments, heart, liver, and kidney disease,

The Social Security Administration has several functions, the main one being to provide financial assistant to patients with a disability that will be unable to work for a period of twelve months or more. This requirement is usually met by individuals who have been diagnosed with prostate cancer.

Mitochondrial cytopathy is a genetic heritable disorder [5]. It occurs as a result of DNA mutation in the gem-line cells that can be transmitted to the second generation. This type of genetic disorder is often caused by mutations in the mitochondrial DMA versus the nucleic DNA. The mitochondria DNA is 20-30 times more susceptible to acquire mutations secondary to absence of DNA repair mechanisms in the mitochondria, giving rise to frequent point mutations or deletions in the mtDNA during cell division[1]. Such mutations are inherited exclusively from the maternal mitochondria. The paternal mitochondria do not contribute to the fetal mitochondria [6]. When some of the mitochondria in the ovum have mutations in their DNA, some of those defected mitochondria will go to daughter cells upon division. If the cells receiving the defected mtDNA contribute to forming tissues that are actively dividing after birth, they will be eliminated by the natural selection process after successive cell divisions. In contrast, if the cells inheriting the defected mitochondria developed into organs or tissues of limited dividing ability, this will result in problems related to energy metabolism in that organ [6]. Due to the random nature of the process, defected mitochondria may end up randomly in different types of tissue and at different concentration. This explains the variations in the manifestation, progression, prognosis and severity of the disorder.

Further research alludes to the fact that this may be the first study which demonstrates increased mitochondrial function as caused by the bacterium’s polysaccharide outer capsule. Researchers are in the process of synthesizing drugs that could potentially protect the mitochondria and greatly diminish cell death, as well as bacterial replication by blocking the effects of the outer capsule. This particular group intends on advancing their study of drugs to mice and to observe its

Fig. 5 A. Mean number of mitochondria/µm2 ± SEM within 80 µm of the soma for wildtype mitochondria (WT - red) and Rett syndrome mitochondria (RTT – blue), both after 10 days in vitro. B. Mean number of mitochondria/µm2 ± SEM within 16-32, 32-48, 48-64 and 64-80 µm of the soma for wildtype

Consequently, there are many methods to measure mitochondrial function. In this study, many methods were used to confirm the hypothesis of mitochondria dysfunction in HG medium, some of the methods procedures were long and complex. However, one of the easiest way to confirm mitochondrial dysfunction is to measure the ability of mitochondria to make the ATP. Absence of ATP mean mitochondrial dysfunction. This method might be enough to confirm the hypothesis of the

Mitochondria are the powerhouses of every cell in our bodies. According to the United Mitochondrial Disease Foundation, the mitochondrial produce most of the energy for the body (United Mitochondrial Disease Foundation). When this process is interrupted or does not take place then cellular damage begins to occur (United Mitochondrial Disease Foundation). Rolf Luft, Lars Ernster, and Bjorn Afzelius are credited with the first diagnosis of mitochondrial disease via muscle biopsy in 1962 (DiMauro, 2011). Succinctly, it is a “defect in the respiratory chain (DiMauro, 2011)”. Since mitochondria are in every cell in the body, and cells are specialized to the organ system to which they belong, the disease will manifest different symptoms in different individuals based on the organ system(s) affected (United Mitochondrial Disease Foundation). Symptoms can be present from every organ system, however, depending upon the actual genetic encoding affecting the mitochondrial can determine which disease classification a patient may fall within (DiMauro, 2011), (United Mitochondrial Disease Foundation).

Primary role of the mitochondria is that, the main function of mitochondria is the making the energy during the production of adenosine triphosphate (ATP) and through the TCA Cycle (which is also as the Krebs cycle and the Citric Acid Cycle). Mitochondria make about 90% of a cell's energy, and in addition to hold their own genomes in the format in a double-stranded circular molecule called mitochondrial DNA (mtDNA). This is also known determine the cause and effect of oxidative stress to be damaging. This will be useful for this class to explore issues relating to mitochondrial DNA integrity and how it can be damaged, repaired, mutated, and compromised in human

Rhodamine is a lipophilic, cationic dye that accumulates in the mitochondrial matrix because of its charge and solubility in both the inner mitochondrial membrane and matrix space (Scaduto and Grotyohann, 1999). The major limitation for using rhodamine 123 is that when the membrane potential is lost the rhodamine 123 no longer accumulates in the mitochondria so there is no signal. MitoTracker probes label mitochondria similarly to rhodamine 123; however, MitoTracker is also chemically reactive and links to thiol groups in the mitochondria (Chazotte, 2011). Since it is linked to the thiol groups MitoTracker maintains its location and fluorescence intensity after fixation.

“With an estimation of 1 in 4,000 children born with a mitochondrial disease resulting in; deafness, blindness, diabetes, muscle weakness, heart, kidney, and liver failure.”2 Mitochondrial dysfunction has is a significant cause of a number of serious multi-organ diseases due to mutations in mitochondrial DNA (mtDNA) or in nuclear genes involved in mitochondrial function. Preimplantation genetic diagnosis (PGD), a commonly used technique to detect mutations in nuclear DNA,is used to determine levels of mtDNA in embryos. Mitochondrial DNA is strictly maternally inherited, generates most of a cell’s energy, and performs other functions that keep cells healthy. “Each mitochondria has a circle of DNA containing

Several mitochondrial diseases such as chronic progressive external ophthalmoplegia (CPEO), Kearns- Sayre syndrome (KSS), the syndrome of neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP), as well as LS, LHON, MERRF, and MELAS manifest in childhood and have limited therapeutic options. Mitochondrial protein dysfunction has also been linked with varying degrees of evidence to Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) (Lin and Beal, 2006; Trushina and McMurray, 2007), schizophrenia, and autism (Manji et al., 2012; Rossignol and Frye, 2012). Acquired mitochondrial disorders are represented in certain cancers (Wallace, 2012) and metabolic disorders (Nasrallah and Horvath, 2014). For example, mutations in the mitochondrial form of superoxide dismutase SOD1, which functions to protect mitochondria from superoxide damage, is linked to the progression of ALS; (Vehvilainen et al., 2014) NADH dehydrogenase 4 to LHON; (Kornmann, 2013) PARKIN to the familial form of PD;(Schmidt et al., 2010) and TCA cycle enzymes to oncogenesis (Schaefer et al.,

Mitochondria are responsible for producing over 90% of the energy needed to susutain life. When mitochondria fail, less and less energy is generated within our cells, this is mitochondrial disease. This disease can be attributed to mitochondrial mutations. It is estimated that between 10-15 people I every 100,000 people are affected – (these figures have been taken from berg biochemistry).

In pancreas cells, the mtDNA depletion can contribute to the age-related decline in insulin secretory capacity in man [55]. Also, the immunoreactivities of many mitochondrial enzymes, such as cytochrome oxidase, an important enzyme located on the inner mitochondrial membrane and a component of aerobic metabolism, respiratory chain and ATP synthetase complex, decrease when the age-related mitochondrial bioenergetics happens [42]. The extent of decrease or loss of this enzyme represents the loss of bioenergetic capacity [48]. As it was mentioned before, these age-related mitochondrial defects can all be detected by histochemical staining of MTCO1, which is an important biomarkers of mitochondrial function. Besides, the oxidative damage can trigger the release of intermembrane space proteins, such as cytochrome c (cyt c) into the cytosol and opening of the permeability of transition pore, causing a cascade of cell apoptosis [53,

Mitochondria are important intracellular organelles responsible for life & death. The mitochondrial matrix has multiple copies of mitochondrial DNA whose replication are not related to the cell cycle. Thus replication of mitochondrial DNA occurs several times and leads to mutations due to error in replication. This leads to mitochondrial dysfunctions which subsequently leads to oxidative stress and an increase in ROS . The main function of mitochondria is to produce ATP by oxidative phosphorylation. It regulates a variety of metabolic and signaling pathways and also plays an important role in programmed cell death. Recent studies using animal models have shown the decline in mitochondrial function with age thus bringing out a relationship between mitochondrial dysfunction and

Accumulation of DNA damage occurs with increasing age, causing cells to deteriorate and malfunction. While DNA damages incur constantly in cells of living organisms, most of the damages are repaired in healthy individuals. However, some DNA damage accumulate as the DNA polymerases and other repair mechanisms cannot correct defects at a rapid enough pace as the rate of damage. In particular, damage to mitochondrial DNA may lead to mitochondrial dysfunction. Maintenance of metabolic homeostasis along with appropriate stress responses absolutely requires proper mitochondrial function. Mitochondrial dysfunction is known to play a critical role in aging and as well as other numerous human diseases, for example cancer and neurodegenerative disorders